The present invention relates to a method of calibrating measurements in a mass spectrometer or ion mobility spectrometer by analysing reference ions.
It is often desired to update the ion mass or mobility calibration during a mass or ion mobility spectrometry experiment or to check other performance characteristics of the instrument. By way of example, temperature fluctuations can affect the mass measurements in a time of flight (TOF) mass spectrometer indirectly through the affect on the power supply and more directly by causing expansion or contraction of the metal in the flight tube. It is desired to calibrate the instrument in order to obtain accurate measurements even in the presence of such fluctuations. A known and extremely effective means of recovering accurate mass measurements in such an arrangement is to use single point lock mass correction. In lock mass corrections, reference ions of known mass are introduced into the mass spectrometer and analysed in order to calibrate the mass measurements. However, conventional implementations of this lock mass acquisition suffer from a variety of drawbacks, as discussed below.
It is possible to use internal or external reference compounds in order to introduce reference ions into the mass spectrometer. Internal reference techniques refer to acquisitions in which a reference compound is measured in arrays that also contain analyte data. In contrast, external reference techniques acquire separate reference data and analyte data arrays.
In internal reference techniques, the reference compound must be present with the analyte. A reference compound may be mixed into the analyte prior to ionisation, or the reference may be a background ion already present in the analyte sample. In either event, the reference compound may compete for the available charge during the ionisation process. This can lead to the signal from the reference ions being suppressed to the point at which the calibration or correction becomes impossible or inaccurate due to ion statistics or interferences. This problem can be circumvented by using an ion source that is separate to the analyte ions source in order to introduce the reference ions into the system. However this inevitably adds complexity and possible points of failure (for example fluidics or pumping requirements) to the instrument. Furthermore, if an analyte has a mass to charge ratio and/or ion mobility that is similar to that of the reference ion, then both the reference ion and analyte ion measurements become compromised.
In external reference techniques, it is usual to interpose acquisition of reference data between analyte data. This often means that analyte data is lost whilst acquiring the reference data. This is obviously undesirable in a quantitative experiment or, for example, when accurate measurement of the position of a chromatographic peak is required. The use of an external reference also requires a mechanism capable of switching the acquisition between analyte and reference modes. This may introduce mechanical complexity or the need for a secondary ion source in order to ionise the reference compound.
It is therefore desired to provide an improved method of mass spectrometry and an improved mass spectrometer.